• The large-molecular-weight activation product C3b of C3, the third component of complement, loses its opsonic properties when it is free in solution (fluid phase) rather than attached to a particle, eg, a bacterial cell. Human fluid-phase C3b, which has been shown in vitro to be an inhibitor of the bactericidal function of human neutrophils, was injected intradermally or intraperitoneally into guinea pigs along with various species of bacteria, and the clearance rate of the bacteria was measured. The injected C3b caused a large increase in the time required for the clearance of the bacteria. The inhibition by C3b of clearance of the injected bacteria was dependent on the bacterial species; bacteria that depended strongly on complement for opsonophagocytosis was cleared at a much lower rate in the presence of fluid-phase C3b than were bacteria that did not have the corresponding dependence on complement.